Preter Klein Panic disorder theory now available on PubMed Central (PMC)

Posted on October 2, 2015 by Maurice Preter MD

[nihms] Manuscript #585187: Your manuscript is available in PMC

Dear Maurice Preter,

Manuscript NIHMS585187 (“Lifelong opioidergic vulnerability through early life separation: A recent extension of the false suffocation alarm theory of panic disorder”) has been loaded into PubMed Central (PMC) and made available for public access:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195810

The submission process for this manuscript is now complete.

We encourage you to make further manuscript submissions as they become eligible. As always, please feel free to contact the NIHMS Help Desk with any questions at http://www.nihms.nih.gov/db/sub.cgi?page=email.

Thank you for using the NIHMS system.

Sincerely,

The NIHMS Help Desk

Panic disorder theory (excerpt):

“In conclusion, we objectively, experimentally showed a physiological link between endogenous opioid system deficiency and panic-like suffocation sensitivity in healthy adults. This is consonant with the expanded Suffocation-False Alarm theory of panic suggesting an episodic functional endogenous opioid deficit (Preter and Klein, 1998). The specificity of the naloxone+lactate model of clinical panic should be tested using specific anti-panic components, possibly including opioidergic mixed agonist-antagonists such as buprenorphine. If specific, the naloxone+lactate effect in normal humans affords a screening method for testing putative anti-panic drugs which is currently not available. This could obviate the experimental treatment of panic disorder patients in drug development.

Our data also show for the first time that actual separations and losses during childhood, such parental death, parental separation or divorce (CPL), effect lifelong alterations in the physiological reactivity of the endogenous opioid system of healthy adults.

This result encourages epigenetic inquiry into the effects of CPL on endogenous opioid systems, and their role in resilience under extreme stress. In addition, a redefinition of what constitutes a (truly) healthy control in clinical research protocols may be called for.”

 

 

Posted in Events, Health, keto, News, Psychiatry/Neurology | Tagged , , , , , |

Neuroprotective and disease-modifying effects of the ketogenic diet

Posted on June 28, 2015 by Maurice Preter MD
PMCID: PMC2367001
NIHMSID: NIHMS42857

Neuroprotective and disease-modifying effects of the ketogenic diet

The publisher’s final edited version of this article is available at Behav Pharmacol
See other articles in PMC that cite the published article.

Abstract

The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models and isolated cells that show that ketone bodies, especially β-hydroxybutyrate, confer neuroprotection against diverse types of cellular injury. This review summarizes the experimental, epidemiological and clinical evidence indicating that the ketogenic diet could have beneficial effects in a broad range of brain disorders characterized by the death of neurons. Although the mechanisms are not yet well defined, it is plausible that neuroprotection results from enhanced neuronal energy reserves, which improve the ability of neurons to resist metabolic challenges, and possibly through other actions including antioxidant and anti-inflammatory effects. As the underlying mechanisms become better understood, it will be possible to develop alternative strategies that produce similar or even improved therapeutic effects without the need for exposure to an unpalatable and unhealthy, high-fat diet.

Keywords: Alzheimer’s disease, cellular energetics, epilepsy, ketone bodies, ketogenic diet, mitochondria, neuroprotection, Parkinson’s disease, stroke, traumatic brain injury
Posted in Aging, China, dietary, epigenetics, Events, Fifth Avenue Concierge Medicine, Forensic Neuropsychiatry, Health, keto, News, Psychiatry/Neurology | Tagged , , , , , , , , |

Risk factors for progression of brain atrophy in aging: six-year follow-up of normal subjects.

Posted on June 26, 2015 by Maurice Preter MD

Neurology. 2005 May 24;64(10):1704-11.

Risk factors for progression of brain atrophy in aging: six-year follow-up of normal subjects.

Abstract

OBJECTIVES:

To determine the rate of brain atrophy in neurologically asymptomatic elderly and to investigate the impact of baseline variables including conventional cerebrovascular risk factors, APOE epsilon4, and white matter hyperintensity (WMH) on its progression.

METHODS:

We assessed the brain parenchymal fraction at baseline and subsequent annual brain volume changes over 6 years for 201 participants (F/M = 96/105; 59.8 +/- 5.9 years) in the Austrian Stroke Prevention Study from 1.5-T MRI scans using SIENA (structural image evaluation using normalization of atrophy)/SIENAX (an adaptation of SIENA for cross-sectional measurement)(www.fmrib.ox.ac.uk/fsl). Hypertension, cardiac disease, diabetes mellitus, smoking, and regular alcohol intake were present in 64 (31.8%), 60 (29.9%), 5 (2.5%), 70 (39.3%), and 40 (20.7%) subjects, respectively. Plasma levels of fasting glucose (93.7 +/- 18.6 mg/dL), glycated hemoglobin A (HbA1c; 5.6 +/- 0.7%), total cholesterol (228.3 +/- 40.3 mg/dL), and triglycerides (127.0 +/- 75.2 mg/dL) were determined. WMH was rated as absent (n = 56), punctate (n = 120), early confluent (n = 14), and confluent (n = 11).

RESULTS:

The baseline brain parenchymal fraction of the entire cohort was 0.80 +/- 0.02 with a mean annual brain volume change of -0.40 +/- 0.29%. Univariate analysis demonstrated a higher rate of brain atrophy in older subjects (p = 0.0001), in those with higher HbA1c (p = 0.0001), higher body mass index (p = 0.02), high alcohol intake (p = 0.04), severe WMH (p = 0.03), and in APOE epsilon4 carriers (p = 0.07). Multivariate analysis suggested that baseline brain parenchymal fraction, HbA1c, and WMH score explain a major proportion of variance in the rates of brain atrophy in the cohort (corrected R2 = 0.27; p = 0.0001).

CONCLUSIONS:

Neurologically asymptomatic elderly experience continuing brain volume loss, which appears to accelerate with age. Glycated hemoglobin A (HbA1c) was identified as a risk factor for a greater rate of brain atrophy. Clustering of factors associated with the so-called metabolic syndrome in subjects with high HbA1c suggests a link between this syndrome and late-life brain tissue loss.

PMID:

 

15911795

 

[PubMed – indexed for MEDLINE] 
Posted in Aging, China, dietary, epigenetics, Events, Fifth Avenue Concierge Medicine, Forensic Neuropsychiatry, Health, keto, News, Psychiatry/Neurology | Tagged , , , , |

Hyperglycemia is associated with subtle brain injury and impaired attention and memory even in young adults

Posted on June 26, 2015 by Maurice Preter MD
Neurology. 2015 Jun 9;84(23):2329-37. doi: 10.1212/WNL.0000000000001655. Epub 2015 May 6.

Glucose indices are associated with cognitive and structural brain measures in young adults.

Abstract

OBJECTIVE:

To evaluate the possible early consequences of impaired glucose metabolism on the brain by assessing the relationship of diabetes, fasting blood glucose (FBG) levels, and insulin resistance with cognitive performance and brain integrity in healthy young and middle-aged adults.

METHODS:

The sample included dementia-free participants (mean age 40 ± 9 years; 53% women) of the Framingham Heart Study third-generation cohort with cognitive testing of memory, abstract reasoning, visual perception, attention, and executive function (n = 2,126). In addition, brain MRI examination (n = 1,597) was used to determine white matter, gray matter, and white matter hyperintensity (WMH) volumes and fractional anisotropy measures. We used linear regression models to assess relationships between diabetes, FBG, and insulin resistance with cognition, lobar gray matter, and WMH volumes as well as voxel-based microstructural white matter integrity and gray matter density, adjusting for potential confounders. Mediating effect of brain lesions on the association of diabetes with cognitive performance was also tested.

RESULTS:

Diabetes was associated with worse memory, visual perception, and attention performance; increased WMH; and decreased total cerebral brain and occipital lobar gray matter volumes. The link of diabetes with attention and memory was mediated through occipital and frontal atrophy, and the latter also through hippocampal atrophy. Both diabetes and increased FBG were associated with large areas of reductions in gray matter density and fractional anisotropy on voxel-based analyses.

CONCLUSIONS:

We found that hyperglycemia is associated with subtle brain injury and impaired attention and memory even in young adults, indicating that brain injury is an early manifestation of impaired glucose metabolism.

© 2015 American Academy of Neurology.

PMID:

 

25948725

 

[PubMed – in process]
Posted in Aging, China, dietary, epigenetics, Events, Fifth Avenue Concierge Medicine, Forensic Neuropsychiatry, Health, keto, News, Psychiatry/Neurology | Tagged , , , , , , |

Association between benzodiazepine use and occurrence of benign brain tumors.

Posted on June 26, 2015 by Maurice Preter MD
J Neurol Sci. 2014 Jan 15;336(1-2):8-12. doi: 10.1016/j.jns.2013.11.009. Epub 2013 Nov 16.

An association between benzodiazepine use and occurrence of benign brain tumors.

Abstract

OBJECTIVE:

This study was designed to evaluate the impact of long-term benzodiazepine use on the subsequent risk of benign brain tumor (BBT) or malignant brain tumor (MBT) development.

METHOD:

We used data from the National Health Insurance System of Taiwan. For the study cohort, we identified 62,186 patients who had been prescribed benzodiazepine for at least 2 months between January 1, 2000 and December, 31, 2009. For each of the benzodiazepine cases, we randomly selected one insured person from the non-benzodiazepine cohort with frequency matching sex, age, and year of index date. The non-benzodiazepine cohort comprised 62,050 patients. The related hazard ratios (HRs) and 95% confidence intervals (CIs) of developing brain tumors were investigated.

RESULTS:

The overall BBT incidence rate was 3.33-fold higher in the benzodiazepine cohort than the non-benzodiazepine cohort (46.3 vs 13.9 per 100,000 person-years) with an adjusted HR of 3.15 (95% CI=2.37-4.20). Similarly, the MBT incidence rate was 84% higher in the benzodiazepine cohort (3.71 vs 2.02 per 1000 person-years), and the adjusted HR of 1.21 (95% CI=0.52-2.81) was not statistically significant. When compared with the non-benzodiazepine cohort, the adjusted HRs of BBTs increased with benzodiazepine dosage (adjusted HR=2.12, 95% CI=1.45-3.10, for 36-150 mg/year; adjusted HR=7.03, 95% CI=5.19-9.51, for ≥151 mg/year).

CONCLUSION:

In this population-based study, we found a significant increase in the risk of benign brain tumor development in a cohort of long-term BZD users.

Copyright © 2013 Elsevier B.V. All rights reserved.

KEYWORDS:

Benign brain tumor (BBT); Benzodiazepine; Cohort study; Malignant brain tumor (MBT); National Health Insurance System; Population-based

PMID:

 

24314718

 

[PubMed – indexed for MEDLINE] 
Icon for Elsevier Science
Posted in Aging, epigenetics, Events, Fifth Avenue Concierge Medicine, Forensic Neuropsychiatry, Health, keto, News, Psychiatry/Neurology | Tagged , , , |